Among the most serious complications of the disease diabetes are the occurrence of retinal and glomerular lesions. There is much histochemical and chemical evidence to indicate that these lesions are glycoprotein in nature. However, much remains to be learned of the types, carbohydrate composition and structure of the glyco-proteins in these lesions and of the possible alterations in glycoprotein metabolism which bring them about. The overall aim of this research project is to investigate the nature and metabolic basis for the glycoprotein alterations in diabetes, particularly those which result in a thicking of the basement membrane of the kidney. The main questions to be answered are the following: 1. Are there differences in types and amount of glycoproteins in the basement membranes of diabetic animals and what are these differences? 2. What possible alterations in glycoprotein metabolism in diabetes are responsible for the occurrence of the basement membrane lesions? 3. Are changes in the metabolism of glycoproteins in the diabetic state more pronounced in the glomerulus where basement membrane thicking is prominent than in the tubules where pathological changes are much less server? 4. What effect do hormonal and pharmacologic agents have on glycoprotein metabolism and on the development of diabetic lesions? The answers to these questions will be sought by an investigation of the metabolism and synthesis of basement membrane compounds in isolated glomeruli and tubules from normal and diabetic animals.